Analysis of the expression of immune response genes in T cells, B cells, and antigen presenting cells. Study of the mechanism of action of the thymus on the development of T cell repertoire for antigen recognition and self-recognition. Experiments on the ontogeny of antigen presenting cells and their turnover in spleen, peritoneal cavity, and thymus. Selected Highlights of Work Completed This Year: I. Gene Complementation: We have demonstrated that the genes which control the responsiveness to a given antigen need not be present in the genome of the responding T cell as long as it has matured in an environment in which the gene was present (Longo & Schwartz:J.Exp.Med., in press). We have also demonstrated that the mechanism by which a genetic nonresponder T cell "learns" to respond to a given antigen is by developing a receptor for the antigen in conjunction with immune response gene products on the surface of the antigen presenting cell, i.e., the T cell sees both structures, antigen and Ir gene products (Longo & Schwartz: Proc.Natl.Acad.Sci., in press). We have further shown that the alteration in the T cell receptor repertoire which occurs in the thymus may be caused by antigen presenting cells in the thymus. These thymic antigen presenting cells may determine what the T cell emerging from the thymus is capable of doing (Longo & Schwartz: Nature, in press). Further studies have examined the celluar requirements for mounting an antibody response to T-independent antigens, of which the pneumococcal polysaccharide vaccine is an example (Kirkland et al: J. Immunol.).